Scattering of light by ZnO nanorod arrays.

The optical properties of ZnO nanorod (NR) arrays were investigated by optical total transmittance (TT) and diffuse reflectance (DR) spectroscopy in the visible region. The NRs were grown electrochemically in a three-electrode cell over a glass/fluorine-doped tin oxide (FTO) substrate. The mean length, radius, and density of NR samples were characterized by scanning electron microscopy. The results were correlated with the observed optical properties. Since light scattering for these NR arrays is highly dependent on their morphology, therefore, a model for light scattering based in the Mie theory for cylinders was implemented to understand the observed spectra. The mean scattering and extinction cross sections were calculated from the morphology of the samples. They were used to fit the DR spectra. From the fittings, the TT spectra of the samples could be calculated. A good agreement with the experimental results was obtained. This indicates that the implemented model represents well the observed scattering phenomena.

High ultrasensitive serum C-reactive protein may be related to freezing of gait in Parkinson's disease patients.

C-reactive protein (CRP) is a biomarker of systemic inflammation that has been linked to accelerated decline in walking speed in older adults. The aim of the present study was to compare the CRP levels of PD patients with vs patients without freezing of gait (FOG). Patients and controls participating in the COPPADIS-2015 study that performed blood extraction for determining molecular serum biomarkers were included. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the Freezing of Gait Questionnaire (FOG-Q). Immunoassay was used for determining ultrasensitive CRP (US-CRP) level (mg/dL). In the PD group (n = 225; 61.8 ± 9.5 years old, 61.8% males), 32% of the patients presented FOG but none in the control group (n = 65; 60.3 ± 6.1 years old, 56.9% males) (p < 0.0001). Differences in US-CRP level were significant in patients with FOG vs patients without FOG and vs controls (0.31 ± 0.52 vs 0.16 ± 0.21 vs 0.21 ± 0.22; p = 0.04). Significant differences were also observed between patients with vs without FOG (p = 0.001) but not between patients and controls (p = 0.163). US-CRP level was related to FOG (OR = 4.369; 95% CI 1.105-17.275; p = 0.036) along with H&Y (OR = 2.974; 95% CI 1.113-7.943; p = 0.030) and non-motor symptoms burden (NMSS total score; OR = 1.017; 95% CI 1.005-1.029; p = 0.006) after adjusting for age, gender, disease duration, equivalent daily levodopa dose, number of non-antiparkinsonian drugs per day, motor fluctuations, cognition, motor phenotype, and chronic use of anti-inflammatory drugs. The present study suggests that serum US-CRP level is related to FOG in PD patients. Inflammation could be linked to FOG development.

Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of Alzheimer's disease during lifespan.

Alzheimer's disease (AD) is the most common form of dementia and one of the major causes of disability and dependency in older people. Accumulating evidences link gut microbiota with different diseases and its relationship with neurodegenerative diseases is becoming most intriguing. This study was aimed to compare the gut microbiota of transgenic APP/PS1 (TG) mice, a well-established deterministic mouse model of AD, with their C57BL/6 wild-type (WT) littermates. Faecal samples were collected from 3-, 6- and 24-month-old mice and analysed by pyrosequencing of the V1-V3 region of the bacterial 16S rRNA genes. Bacterial profiles were similar in all young mice (3 months old), and started to diverge so that 6-month-old WT and TG mice had different and more diverse microbiota. During ageing, Turicibacteriaceae (typical mice bacterial group) and Rikenellaceae increased in all groups, although total Bacteroidetes remained stable. TG mice were characterized by an increase in Proteobacteria after 6 months, particularly the genus Sutterella (Betaproteobacteria), interestingly also increased in autism disorder. Also, the inflammation related family Erysipelotrichaceae was more abundant in TG mice at 24 months compared to wild-type control. In summary, AD pathology in mice shifts the gut microbiota towards profiles that share features with autism and inflammatory disorders. SIGNIFICANCE AND IMPACT OF THE STUDY: Alzheimer's disease is a neurodegenerative disease and neuroinflammation in the central nervous system appears to have a pivotal role. Using the transgenic APP/PS1 (TG) mouse model, we successfully characterized how AD pathology shifted gut microbiota composition during ageing towards an inflammation related bacterial profile related to Proteobacteria and Erysipelotrichaceae and suggest that these changes could contribute to disease progression and severity. Microbiota-targeted interventions could therefore represent a strategy to postpone disease symptoms.

Alexandrite Laser for the Treatment of Resistant and Hypertrophic Port Wine Stains: A Clinical, Histological and Histochemical Study.

BACKGROUND: Port wine stains (PWSs) are commonly treated by the pulsed dye laser. However, treatment of hypertrophic or resistant PWSs is a major therapeutic challenge. The long-pulsed Alexandrite laser could be a safe and effective treatment for resistant PWSs, due to an increase depth of penetration of 50-75% over PDL. OBJECTIVE: The aim of this study was to assess the efficacy and safety of a long-pulsed Alexandrite laser in patients with hypertrophic, dark and/or resistant PWSs. Pink pale resistant PWS were excluded from the study. METHODS: Twenty-one patients (age 20-75 years), phototypes I-IV on the Fitzpatrick scale, with PDL dark resistant PWSs were treated with long-pulsed Alexandrite laser. We excluded high phototypes and PDL pink resistant PWSs. All patients were treated with 3 laser sessions at settings of 3-ms pulse duration, 10-mm spot, 35-55J/cm(2), with cooling (Dynamic Cooling Device 50ms with delay 30ms). Laser sessions were repeated approximately every 2 months. Three dermatologists evaluated treatment effectiveness by means of photographs of the patients before and after laser treatment (scale from 0 to 4). Adverse events were registered. Patient satisfaction was also assessed (scale from 0 to 10). RESULTS: Mean global improvement was rated as 2.28. Long-lasting side effects included minimal scarring after blistering in 1 patient. Mean patient satisfaction was 8.5. CONCLUSIONS: Our study concludes that long-pulsed Alexandrite laser was effective for treatment of resistant PWSs, although the therapeutical window is narrow with this treatment.

Histochemical Evaluation of the Vessel Wall Destruction and Selectivity After Treatment with Intense Pulsed Light in Capillary Malformations.

BACKGROUND: Among the different approaches for improving the effectiveness in the treatment of Capillary Malformations type Port Wine Stain (CM type PWS) are the intense pulsed light sources. There are few clinical studies prove useful in the treatment of CM. Furthermore, no studies have been published yet demonstrating the histological effects of IPL in CM. OBJECTIVES: To assess the histological effects of pulsed light in capillary malformations type port wine stain. We wanted to compare epidermal, dermal and vessel wall damage after treatment with different combinations of IPL parameters. MATERIAL AND METHODS: Fifty-five post-treatment biopsies were performed in 15 consenting patients with CM and stained with nitroblue-tetrazolium chloride (NBTC). Patients had not been treated previously. RESULTS: Fifteen patients with CM, with a median age of 39 years-old were enrolled in this study. In this series, the patients with the most severe epidermal damage were those with a darker phototype. Pink CM were especially resistant to treatment, even using high fluences, short pulse durations and stacking pulses. Longer intra- and interpulse delays were effective in purple CM, achieving adequate vessel destruction. CONCLUSIONS: IPL devices provide a vast amount of treatment possibilities and further studies are necessary to optimize therapeutic approaches to CM. In this study we have observed the histological effects of different pulses on the MC type PWS.

Effect of 3 Weeks Use of Compression Garments on Stride and Impact Shock during a Fatiguing Run.

Excessive and prolonged exposure to impact acceleration during running is associated with increased injury rate. Acute use of compressive garments has been speculated to improve attenuation. However, it is unknown how longer interventions of compressive garments influence attenuation in running. 40 runners trained with compressive and placebo stockings for 3 weeks. Perception of comfort, stride parameters (rate, length) and impact acceleration (head and tibial peak acceleration, magnitude, acceleration rate and attenuation) were measured every 5 min during a fatigue run (30 min at 80% of the individual's maximal aerobic speed). Compressive stockings reduced tibial peak acceleration and magnitude compared to placebo stockings at every minute (p<0.05) except for the initial measurement (p>0.05). Moreover, compressive stockings led to a lower rate of increase in tibial peak acceleration (14%, p<0.005) and magnitude (16%, p<0.001) as a result of the development of fatigue compared to placebo stockings (24% and 26% increase, p=0.014 and p=0.003, respectively). Similar perception of comfort was reported for both garments. Training with compressive stockings for 3 weeks reduced impact acceleration and the rate of increase in acceleration compared to placebo stockings. These findings suggest that compressive stockings may play a protective role by reducing impact accelerations during running.

Effects of graduated compression stockings on skin temperature after running.

High skin temperatures reduce the thermal gradient between the core and the skin and they can lead to a reduction in performance and increased risk of injury. Graduated compression stockings have become popular among runners in the last years and their use may influence the athlete's thermoregulation. The aim of this study was to investigate the effects of graduated compression stockings on skin temperature during running in a moderate indoor environment. Forty-four runners performed two running tests lasting 30min (10min of warm-up and 20min at 75% of their maximal aerobic speed) with and without graduated compressive stockings. Skin temperature was measured in 12 regions of interest on the lower limb by infrared thermography before and after running. Heart rate and perception of fatigue were assessed during the last minute of the running test. Compression stockings resulted in greater increase of temperature (p=0.002 and ES=2.2, 95% CI [0.11-0.45°C]) not only in the body regions in contact (tibialis anterior, ankle anterior and gastrocnemius) but also in the body regions that were not in contact with the garment (vastus lateralis, abductor and semitendinosus). No differences were observed between conditions in heart rate and perception of fatigue (p>0.05 and ES<0.8). In conclusion, running with graduated compression stockings produces a greater increase of skin temperature without modifying the athlete's heart rate and perception of fatigue.

Long-term effects of graduated compression stockings on cardiorespiratory performance.

The use of graduated compression stockings (GCS) in sport has been increasing in the last years due to their potential positive effects for athletes. However, there is little evidence to support whether these types of garments actually improve cardiorespiratory performance. The aim of this study was to examine the cardiorespiratory responses of GCS during running after three weeks of regular use. Twenty recreational runners performed three tests on different days: test 1) - a 5-min maximal effort run in order to determine the participants' maximal aerobic speed; and tests 2) and 3) - a fatigue running test of 30 minutes at 80% of their maximal aerobic speed with either GCS or PLACEBO stockings at random. Cardiorespiratory parameters (minute ventilation, heart rate, relative oxygen consumption, relative carbon dioxide production, ventilatory equivalents for oxygen and carbon dioxide, and oxygen pulse) were measured. Before each test in the laboratory, the participants trained with the randomly assigned stockings (GCS or PLACEBO) for three weeks. No significant differences between GCS and PLACEBO were found in any of the cardiorespiratory parameters. In conclusion, the present study provides evidence that running with GCS for three weeks does not influence cardiorespiratory parameters in recreational runners.

Supplemental L-arginine and vitamins E and C preserve xanthine oxidase activity in the lung of broiler chickens grown under hypobaric hypoxia.

The effects of l-Arg, vitamin C (VC), and vitamin E (VE) on xanthine- (XO) and NAD(P)H-oxidase (NOX) activities, and nitric oxide (NO) availability of hypoxic broilers were evaluated. Chickens were kept in wire cages with free access to feed and water. One-day-old chicks were assigned to 1 of 3 diets: control (CTL; ME 3,200 kcal/kg, CP 23%), high Arg (HA; CTL + Arg 0.8%), or high Arg plus VE and VC (AEC; HA + 200 IU of VE/kg of feed + 500 mg of VC/L of water), and grown under hypobaric hypoxia (HYP) from d 7 to 30. A fourth group of birds was fed the CTL diet and grown under normoxia (CTL-NOR). At d 30, chickens were euthanized, their lungs fixed in vivo, excised, and processed for cyto- and histochemistry. The enzymes XO and NOX were localized and activities assessed histochemically and in lung homogenates. The NO depletion was assessed through nitrotyrosine immunocytochemistry colloidal gold particles (NTY). The XO and NOX localized in cell membranes and within vesicles of pulmonary vessel endothelial cells. The XO activity was higher in CTL-NOR birds (586 ± 43 reflectance units) than in both AEC-HYP (456 ± 39) and HA-HYP birds (394 ± 31), whereas CTL-HYP birds had the lowest XO activity (313 ± 27). The NO depletion was not affected by dietary or hypoxia conditions in clinically healthy birds; nevertheless, hypoxic birds that developed pulmonary hypertension had higher NTY levels (less NO, 145 ± 19) than hypoxic but clinically healthy birds (56 ± 11). Thus, the concurrent supplementation of Arg, VE, and VC restored XO activity without affecting NOX activity or NO availability. The dual role of XO, which produces superoxide and uric acid, may have buffered the effects of superoxide in broiler chickens grown under hypobaric hypoxia.

Effects of distance and barriers between resources on bone and tendon strength and productive performance of broiler chickens.

Lameness or leg weakness is becoming an important problem in broilers selected for rapid growth, and although the causes are not known, sedentary behavior could be a cause. Two experiments were conducted to study the effects of distance and the presence of ramps between resources (feed and water) on bone and tendon strength, ability to stand, and productive performance. In experiment 1, straight run Ross 708 chicks (n = 1,260) were randomly assigned to 1 of 3 treatments: 1.0, 3.3, or 6.6 m between resources (6 pen replicates/treatment). In experiment 2, Cobb 500 male chicks (n = 864) were randomly assigned to 1 of 4 treatments (2 × 2 factorial, 4 pen replications/treatment) consisting of 2 distances (3 or 8 m) with (WR) or without (NR) a ramp (a triangular prism 31 cm high and 132 cm wide at the base). At d 21, 45, and 56 (experiment 1), or at d 28, 35, 42, and 49 (experiment 2), birds were weighed, killed, and tibias collected to measure breaking strength (BBS), and abdominal fat (AbF) content. At d 49 (experiment 2), calcaneus tendons were also collected to measure breaking strength (TBS). Foot pad lesions and latency to lie (LTL) were determined before killing the birds. In experiment 1, distance did not affect BBS, LTL, foot pad lesions, or BW, but at d 49, birds in the 6.6 m treatment had lower AbF than birds in the other treatments. In experiment 2 at d 49, birds in the 8 m treatment tended to have a higher BBS than birds in the 3 m treatment (P = 0.09), whereas WR birds had lower tendon breaking strength than NR birds (P < 0.01); however, LTL was highest in 8-m NR birds. Final BW was not affected by distance, but birds in the NR group were heavier than birds in the WR group. Furthermore, AbF was lower in 8 m than in 3 m birds. Our results suggest that longer distances between resources have limited effects on bone strength, but increase the LTL, and may change feeding patterns and carcass characteristics, as evidenced by the lower AbF content. Ramps or inclination affected tendon breaking strength.

Influence of foot orthosis customisation on perceived comfort during running.

Although running is associated with many health benefits, it also exposes the body to greater risk of injury. Foot orthoses are an effective strategy to prevent such injuries. Comfort is an essential element in orthosis design since any discomfort alters the runner's biomechanics, compromising performance and increasing the risk of injury. The present study analyses the perceived comfort of three types of orthoses: custom-made, prefabricated and original running shoe insoles. Nine comfort variables for each insole were assessed in a sample of 40 runners. Custom-made and prefabricated insoles were both perceived as significantly more comfortable than the original insoles. The differences were clinically relevant and were potentially causes of modifications in running gait. Although the prefabricated insoles were rated slightly higher than the custom-made insoles, the differences were not statistically significant. This study shows that prefabricated insoles constitute a reasonable alternative to custom-made insoles in terms of comfort. PRACTITIONER SUMMARY: The perceived level of comfort of footwear is considered to be a protective measure of the potential risk of running injuries. We here compared runners' perception of comfort of custom-made and prefabricated orthoses while running. We found that even though custom-made orthoses are closely matched to each individual's foot, such customisation does not necessarily imply greater comfort.

Extreme xanthomatosis in patients with both familial hypercholesterolemia and cerebrotendinous xanthomatosis.

Two unrelated individuals were referred to Lipid Clinics in The Netherlands and Chile with extreme xanthomatosis and hypercholesterolemia. Both were diagnosed with heterozygous familial hypercholesterolemia (heFH) after molecular genetic analysis of the low-density lipoprotein (LDL) receptor gene. Since heFH by itself could not account for the massive xanthomas, the presence of an additional hereditary lipid or lipoprotein disorder was suspected. Further genetic analysis revealed homozygozity for mutations in the sterol 27-hydroxylase gene, confirming the diagnosis of cerebrotendinous xanthomatosis (CTX). Markedly, the typical neurological manifestations of CTX were absent, suggestive of a protective role of LDL-receptor deficiency against the severe neurological consequences of CTX.

The Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) study: Subclinical cervico-cerebral stenosis and middle cerebral artery pulsatility index as predictors of long-term incident cognitive impairment.

BACKGROUND AND AIMS: We aimed to study subclinical non-invasive vascular markers as predictors of incident long-term cognitive impairment in a longitudinal population-based study. METHODS: The Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) study is a population-based study that included a random sample of 933 Caucasian subjects (mean age 66 years, 64% male) with a moderate-high vascular risk and without history of stroke or dementia. Subclinical carotid and intracranial stenosis was assessed at baseline visit by cervical and transcranial color-coded duplex (TCCD) and confirmed by magnetic resonance angiography. Cervico-cerebral stenosis (CCS) was defined as the presence of extra and/or intracranial stenosis >50%. Baseline middle cerebral artery pulsatility index (MCA-PI) was measured bilaterally by TCCD, and mean PI of both sides was considered for analyses. Subjects were followed-up to determine incident long-term cognitive impairment (mild cognitive impairment or dementia). RESULTS: After a median of 7.16 [6.91-7.75] years of follow-up, 91 subjects (9.7%) developed cognitive impairment, 27 of them mild cognitive impairment, and 64 dementia. Incidence of cognitive impairment was significantly higher among subjects with subclinical CCS (21.4% versus 9% in those without CCS) and among those with mean MCA-PI>1 (13.5% versus 7.4% in those with MCA-PI<1). In multivariate Cox regression analyses, both CCS and MCA-PI>1 were independently associated with incident cognitive impairment with HR of 2.07 [1.11-3.88] and 1.58 [1.02-2.46], respectively. CONCLUSIONS: Subclinical cervico-cerebral stenosis and higher MCA-PI are non-invasive neurosonological markers of incident long-term cognitive impairment in our population.

Eco-friendly modification of a regenerated cellulose based film by silicon, carbon and N-doped carbon quantum dots.

Modification of a regenerated cellulose thin film by inclusion of different non-toxic nanodots (silicon-dots (SiDs), carbon-dots (CDs)) or nitrogen-doped carbon dots (N-CDs)) by aqueous nanodots solution immersion was performed. Nanodots presence into the cellulosic structure was evidenced by confocal microscopy images at different depth and changes in film mechanical, electrical and optical parameters. Our results reveal that the inclusion of the different nanodots in the cellulosic support increases, indifferent percentages, the mechanical resistance and electrical conductivity of modified films, but they hardly affect light transmittance. Particularly, modification with N-CDs largely favored film conductivity due to the presence of the higher number of charged functional groups (CNH2 and OCNH2) groups) on N-CDs surface, allowin gus the attainment of a flexible, fluorescent and transparent high conductive eco-friendly film. In fact, the non-toxic character of both support-film and nanodots, endorses the use of these new nano-engineering films in biomedical applications.

Effects of prefabricated and custom-made foot orthoses on skin temperature of the foot soles after running.

OBJECTIVE: Foot orthoses are increasingly used by runners despite the controversy about whether their use can reduce the risk of overuse injuries. Some authors have found modifications in plantar pressures with the use of foot orthoses, which could produce changes in the surface skin temperature of the foot soles. The aim of this study was to analyse the effects of custom-made and prefabricated foot orthoses on the skin temperature of different regions of both foot soles after running. APPROACH: Twenty-four participants carried out a maximal aerobic speed test as a pre-test, and three running tests at the laboratory wearing different foot orthoses conditions (control, prefabricated and custom-made) previously randomized. Skin temperature of four regions of interest of the foot soles was assessed before, immediately after and ten minutes after running. MAIN RESULTS: The use of prefabricated and custom-made foot orthoses did not produce changes on skin temperature of the foot soles neither in absolute temperatures (p > 0.05), nor in temperature variations: between immediately after and before running (p > 0.05), and between ten minutes after and immediately after running (p > 0.05). Otherwise, higher values were found with no insoles than with prefabricated foot orthoses, 10 min after running in relation to before running, in forefoot [mean (standard deviation): 5.6 (2.4) versus 3.7 (2.7) °C; p = 0.02; effect size (ESd) = 0.72], midfoot [3.7 (1.5) versus 2.7 (1.5) °C; p = 0.03; ESd = 0.65] and rearfoot [4.18 (2.05) versus 2.9 (1.82) °C; p = 0.02; ESd = 0.64)]. SIGNIFICANCE: In conclusion, the use of foot orthoses, in general, does not affect the surface skin temperature of the foot soles after an intense run.

Circadian serum concentrations of tylosin in broilers after feed or water medication.

1. Because tylosin is a time-dependent antibacterial agent, and because feeding and drinking of broilers decreases in late afternoon and ceases in the dark, it was hypothesised that serum concentrations of this drug are greatly reduced during the dark period. 2. The trial was carried out in a commercial poultry house, under standard broiler husbandry conditions, with food and water withdrawn from 22:00 until 07:00 h next morning and exposed to a natural light cycle of 13L:11D. 3. Broilers were given tylosin tartrate, in either feed or water, for 5 d as follows: 100, 200 and 300 ppm in feed, equivalent to 12.6, 25.2 and 37.8 mg/kg/d, respectively; and 200 and 400 mg/l in drinking water, equivalent to 51 to 102 mg/kg/d, respectively. 4. At 07:00 h on d 4, and for the next 40 h, hourly serum samples were obtained and analysed for tylosin by means of a microbiological assay. 5. Day vs night concentrations of tylosin expressed as area under the curve (AUC) in all groups revealed greater values during the day. The highest AUC and AUC(24)/minimal inhibitory concentration (MIC) ratio were obtained in the group medicated with 400 mg/l and the corresponding lowest values were found in the group medicated with 100 ppm in feed. 6. In conclusion, tylosin did not reach therapeutic serum concentrations during the dark period, at all dose rates tested when administered in feed or water. A sustained release form of this drug is needed to solve this inadequacy of tylosin medication in broilers.

Size-strain separation in diffraction line profile analysis.

Separation of size and strain effects on diffraction line profiles has been studied in a round robin involving laboratory instruments and synchrotron radiation beamlines operating with different radiation, optics, detectors and experimental configurations. The studied sample, an extensively ball milled iron alloy powder, provides an ideal test case, as domain size broadening and strain broadening are of comparable size. The high energy available at some synchrotron radiation beamlines provides the best conditions for an accurate analysis of the line profiles, as the size-strain separation clearly benefits from a large number of Bragg peaks in the pattern; high counts, reliable intensity values in low-absorption conditions, smooth background and data collection at different temperatures also support the possibility to include diffuse scattering in the analysis, for the most reliable assessment of the line broadening effect. However, results of the round robin show that good quality information on domain size distribution and microstrain can also be obtained using standard laboratory equipment, even when patterns include relatively few Bragg peaks, provided that the data are of good quality in terms of high counts and low and smooth background.

Suppression of planar cell polarity signaling and migration in glioblastoma by Nrdp1-mediated Dvl polyubiquitination.

The lethality of the aggressive brain tumor glioblastoma multiforme (GBM) results in part from its strong propensity to invade surrounding normal brain tissue. Although oncogenic drivers such as epidermal growth factor receptor activation and Phosphatase and Tensin homolog inactivation are thought to promote the motility and invasiveness of GBM cells via phosphatidylinostitol 3-kinase activation, other unexplored mechanisms may also contribute to malignancy. Here we demonstrate that several components of the planar cell polarity (PCP) arm of non-canonical Wnt signaling including VANGL1, VANGL2 and FZD7 are transcriptionally upregulated in glioma and correlate with poorer patient outcome. Knockdown of the core PCP pathway component VANGL1 suppresses the motility of GBM cell lines, pointing to an important mechanistic role for this pathway in glioblastoma malignancy. We further observe that restoration of Nrdp1, a RING finger type E3 ubiquitin ligase whose suppression in GBM also correlates with poor prognosis, reduces GBM cell migration and invasiveness by suppressing PCP signaling. Our observations indicate that Nrdp1 physically interacts with the Vangl1 and Vangl2 proteins to mediate the K63-linked polyubiquitination of the Dishevelled, Egl-10 and Pleckstrin (DEP) domain of the Wnt pathway protein Dishevelled (Dvl). Ubiquitination hinders Dvl binding to phosphatidic acid, an interaction necessary for efficient Dvl recruitment to the plasma membrane upon Wnt stimulation of Fzd receptor and for the propagation of downstream signals. We conclude that the PCP pathway contributes significantly to the motility and hence the invasiveness of GBM cells, and that Nrdp1 acts as a negative regulator of PCP signaling by inhibiting Dvl through a novel polyubiquitination mechanism. We propose that the upregulation of core PCP components, together with the loss of the key negative regulator Nrdp1, act coordinately to promote GBM invasiveness and malignancy.